Caffeine improves various aspects of athletic performance in adolescents independent of their 163 C > A CYP1A2 genotypes.

PURPOSE: The purpose of this study was to investigate whether variations in 163 C > A CYP1A2 genotypes (rs 762 551) (AA, AC, and CC) modify the ergogenic effects of caffeine (CAF) on strength, power, muscular endurance, agility, and endurance in adolescent athletes. METHODS: One hundred adolescents (age = 15 ± 2 years) were recruited. Participants ingested CAF (6 mg.kg-1 ) or placebo (PLA, 300 mg of cellulose) 1 hour before performing a sequence of physical tests: handgrip strength, vertical jumps, agility test, sit-ups, push-ups, and the Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). RESULTS: Compared to PLA, CAF enhanced (P < .05) sit-up (CAF = 37 ± 9; PLA = 35 ± 8 repetitions) and push-up repetitions (CAF = 26 ± 11; PLA = 24 ± 11 repetitions), and increased distance covered in Yo-Yo IR1 test (CAF = 1010.4 ± 378.9; PLA = 903.2 ± 325.7 m). There was no influence of CAF on handgrip strength (CAF = 35.1 ± 8.9; PLA = 33.7 ± 8.7 kgf), countermovement jump height (CAF = 49.3 ± 12.6; PLA = 47.9 ± 13.8 cm), spike jump height (CAF = 54.2 ± 13.6; PLA = 52.9 ± 14.5 cm), and time in agility test (CAF = 15.8 ± 1.1; PLA = 15.9 ± 1.3 s, P > .05). When present, the ergogenic effect of CAF was not dependent of genotype. CONCLUSION: CAF improves muscular endurance and aerobic performance in adolescent athletes, regardless of their 163 C > A CYP1A2 genotype.

Rates of and Factors Associated With Placebo Response in Trials of Pharmacotherapies for Nonalcoholic Steatohepatitis: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: It is important to know the extent of the placebo effect in designing randomized controlled trials for patients with nonalcoholic steatohepatitis (NASH), to accurately calculate sample size and define treatment endpoints. METHODS: We performed a systematic review and meta-analysis of the placebo groups from randomized controlled trials of adults with NASH that provided histologic and/or magnetic resonance image-based assessments. We identified trials through a comprehensive search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus, from each database's inception through January 2, 2018. RESULTS: We identified 39 randomized controlled trials, comprising 1463 patients who received placebo. Histologic assessment data (the nonalcoholic fatty liver disease activity scores, NAS) were available from 956 patients; magnetic resonance spectroscopy data were available from 295 patients and magnetic resonance proton density fat fraction measurements from 61 patients. Overall, 25% of patients given placebo had an improvement in NAS by 2 or more points (95% CI, 21%-29%) with a small amount of heterogeneity (I2 = 27%). There were improvements by at least 1 point in steatosis scores of 33% ± 3% of patients, in hepatocyte ballooning scores of 30% ± 3% of patients, in lobular inflammation scores of 32% ± 3% of patients, and in fibrosis scores of 21% ± 3% of patients, with a moderate amount of heterogeneity among trials (I2 range, 51%-63%). Patients given placebo had a statistically significant improvement in NAS (by 0.72 ± 0.19), with a large amount of heterogeneity (I2 = 96%). Univariate and multivariate meta-regression showed that trials with a higher baseline NAS, those conducted in South America, and those in which patients had a decrease in body mass index, were associated with greater improvements in NAS among patients given placebo. Patients given placebo had significant reductions in intrahepatic triglyceride, measured by magnetic resonance spectroscopy (by 1.45% ± 0.54%) with moderate heterogeneity (I2 = 40%), and in magnetic resonance proton density fat fraction (by 2.43 ± 0.89), without heterogeneity (I2 = 0). Mean serum levels of alanine and aspartate aminotransferases decreased significantly (by 11.7 ± 3.8 U/L and 5.9 ± 2.1 U/L, respectively; P < .01 for both). CONCLUSIONS: In a meta-analysis of randomized controlled trials of NASH, patients given placebo have significant histologic, radiologic, and biochemical responses. The placebo response should be considered in designing trials of agents for treatment of NASH.

Spirometric changes in obstructive disease: after all, how much is significant?

OBJECTIVE: To establish the upper limits for changes in FEV1, slow vital capacity (SVC), FVC, and inspiratory capacity (IC) after placebo administration in patients with airflow obstruction. METHODS: One hundred and two adults with airflow obstruction (FEV1 = 62 ± 19% of predicted) were included in the study. All of the participants performed SVC and FVC maneuvers before and after the administration of placebo spray. The changes in FEV1, SVC, FVC, and IC were expressed as absolute values, percentage of change from baseline values, and percentage of predicted values, 95% CIs and 95th percentiles being calculated. Factor analysis was performed in order to determine how those changes clustered. RESULTS: Considering the 95% CIs and 95th percentiles and after rounding the values, we found that the upper limits for a significant response were as follows: FEV1 = 0.20 L, FVC = 0.20 L, SVC = 0.25 L, and IC = 0.30 L (expressed as absolute values); FEV1 = 12%, FVC = 7%, SVC = 10%, and IC = 15% (expressed as percentage of change from baseline values); and FEV1 = 7%, FVC = 6%, SVC = 7%, and IC = 12% (expressed as percentage of predicted values). CONCLUSIONS: In patients with airflow obstruction, IC varies more widely than do FVC and SVC. For IC, values greater than 0.30 L and 15% of change from the baseline value can be considered significant. For FVC, values greater than 0.20 L and 7% of change from the baseline value are significant. Alternatively, changes exceeding 0.20 L and 7% of the predicted value can be considered significant for FEV1 and FVC. On factor analysis, spirometric parameters clustered into three dimensions, expressing changes in flows, volumes, and dynamic hyperinflation.

Alterações espirométricas em doenças obstrutivas: afinal, o quanto é relevante? / Spirometric changes in obstructive disease: after all, how much is significant?

OBJETIVO: Estabelecer os limites superiores para mudanças em VEF1, capacidade vital lenta (CVL), CVF e capacidade inspiratória (CI) após o uso de placebo em pacientes com obstrução ao fluxo aéreo. MÉTODOS: Cento e dois adultos com obstrução ao fluxo aéreo (VEF1 = 62 ± 19% do previsto) foram incluídos neste estudo. Todos os participantes realizaram manobras de CVL e CVF antes e depois do uso de spray de placebo. As mudanças em VEF1, CVL, CVF e CI foram expressas em valores absolutos, porcentagem de variação em relação aos valores basais e porcentagem dos valores previstos, e foram calculados os IC95% e os percentis 95. A análise fatorial foi realizada a fim de determinar como essas alterações se agrupavam. RESULTADOS: Considerando os IC95% e percentis 95 e após o arredondamento dos valores, obtivemos os seguintes limites superiores para resposta significante: VEF1 = 0,20 L, CVF = 0,20 L, CVL = 0,25 L e CI = 0,30 L (em valores absolutos); VEF1 = 12%, CVF = 7%, CVL = 10% e CI = 15% (em porcentagem de variação em relação aos valores basais) e VEF1 = 7%, CVF = 6%, CVL = 7% e CI = 12% (em porcentagem dos valores previstos). CONCLUSÕES: Em pacientes com obstrução ao fluxo aéreo, a CI apresenta maior variabilidade do que a CVF e a CVL. Para a CI, valores maiores que 0,30 L e 15% de variação em relação ao valor basal devem ser considerados significantes. Para CVF, valores maiores que 0,20L e 7% de variação em relação ao valor basal são significantes. Alternativamente, alterações de mais de 0,20 L e 7% do previsto no VEF1 e na CVF devem ser consideradas significantes. Na análise fatorial, os parâmetros espirométricos se agruparam em três dimensões, expressando mudanças no fluxo, volume e hiperinsuflação dinâmica.

OBJECTIVE: To establish the upper limits for changes in FEV1, slow vital capacity (SVC), FVC, and inspiratory capacity (IC) after placebo administration in patients with airflow obstruction. METHODS: One hundred and two adults with airflow obstruction (FEV1 = 62 ± 19% of predicted) were included in the study. All of the participants performed SVC and FVC maneuvers before and after the administration of placebo spray. The changes in FEV1, SVC, FVC, and IC were expressed as absolute values, percentage of change from baseline values, and percentage of predicted values, 95% CIs and 95th percentiles being calculated. Factor analysis was performed in order to determine how those changes clustered. RESULTS: Considering the 95% CIs and 95th percentiles and after rounding the values, we found that the upper limits for a significant response were as follows: FEV1 = 0.20 L, FVC = 0.20 L, SVC = 0.25 L, and IC = 0.30 L (expressed as absolute values); FEV1 = 12%, FVC = 7%, SVC = 10%, and IC = 15% (expressed as percentage of change from baseline values); and FEV1 = 7%, FVC = 6%, SVC = 7%, and IC = 12% (expressed as percentage of predicted values). CONCLUSIONS: In patients with airflow obstruction, IC varies more widely than do FVC and SVC. For IC, values greater than 0.30 L and 15% of change from the baseline value can be considered significant. For FVC, values greater than 0.20 L and 7% of change from the baseline value are significant. Alternatively, changes exceeding 0.20 L and 7% of the predicted value can be considered significant for FEV1 and FVC. On factor analysis, spirometric parameters clustered into three dimensions, expressing changes in flows, volumes, and dynamic hyperinflation.

Estudio clínico de no-inferioridad y de equivalencia: metodología, análisis e interpretación / Non-inferiority and equivalence clinical trials: methodology, analysis and interpretation of the results

Los estudios controlados con placebo son el método ideal para evaluar la eficacia del tratamiento médico. Debido al gran número de tratamientos de comprobada eficacia en ciertas aplicaciones, los estudios controlados con placebo son a menudo poco éticos. Los estudios de no-inferioridad y de equivalencia son apropiados para evaluar la eficacia de un tratamiento experimental versus un control activo cuando se plantea la hipótesis que el tratamiento experimental puede no ser superior a un tratamiento de comprobada eficacia, pero es clínica y estadísticamente no inferior. El diseño y el reporte de estos estudios deben de seguir las recomendaciones del grupo CONSORT. Para tal fin, es indispensable seleccionar un óptimo control activo. La eficacia del control activo debería ser documentada a través de buenos estudios históricos controlados con placebo; a partir de estos datos es indispensable determinar el margen de no-inferioridad. Los resultados del nuevo tratamiento deben ser comparados con el control activo por análisis múltiples, incluyendo el placebo putativo. El término de no-inferioridad es usado cuando se refiere a un estudio de una sola cola (diferencia en respuesta menor que delta); equivalencia cuando se refiere a estudio de dos colas (diferencia en respuesta entre -Δ y +Δ). Para documentar los planteamientos teóricos se recurre a datos de estudios publicados recientemente, relacionados con moléculas eficaces en el control de la presión arterial y en la reducción de los índices de mortalidad en enfermedades cardiovasculares.

Placebo-controlled trials are the ideal for evaluating medical treatment efficacy. Given the large number of proven effective treatment in several areas, placebo-controlled trials are often unethical. The non-inferiority and equivalence trials are appropriate for evaluation of the efficacy of an experimental treatment versus an active control when it is hypothesized that the experimental treatment may not be superior to a proven effective treatment, but is clinically and statistically not inferior in effectiveness. The design and reporting of these studies must follow the CONSORT statements. An active control must be selected. Good historical placebo-controlled trials documenting the efficacy of the active control must exist. From these historical trials, a margin of non-inferiority must be determined. The results of the new treatment must be compared with active control through multiple analysis, including a putative placebo comparison. The term non-inferority is used when referring to a 1-sided trial (difference in response lower than Δ); equivalence, when referring to 2-sided trials (difference in response between-Δ and +Δ). In order to give practical data, results of published trials related to active molecules effective in the control of blood pressure and in reducing mortality in cardiovascular diseases are used.

Reportes y entrevistas del American College of Cardiology: New Orleans 2007 / Report and interviews of the American College of Cardiology: New Orleans 2007

Este documento es publicación de la Canadian Medical Association y revisado por el Dr. Andreas Wieldosz del Hospita de Ottawa. Su contenido tiene propósitos educativos e informativos, sobre las investigaciones más recientes, Está dirigido primordialmente a médicos en atención primaria y se le sugiere al lector consultar las respectivas publicaciones originales e información relacinada, antes de tomar las acciones mencionadas en este reporte.

Influência de bochechos com soluçöes antimicrobianas na inibiçäo da placa dentária e contagem de estreptococos mutans em crianças / Influence of mouthrinses with antimicrobial solutions on the dental plaque inhibition and mutans streptococci counts in children

Avaliou-se, em crianças, o efeito de bochechos diários com soluçäo placebo composta de água deionizada mentolada (Grupo I); gluconato de clorexidina 0,12 por cento associado ao fluoreto de sódio 0,05 por cento (Grupo II); digluconato de clorexidina 0,2 por cento (Grupo III) e esteviosídeo 0,5 por cento associado ao fluoreto de sódio 0,05 por cento pH 3,4 (Grupo IV), sobre a inibiçäo do acúmulo de placa dentária e sobre o nível de estreptococos mutans salivar. Para a verificaçäo do efeito sobre a placa, empregou-se o índice de LOE e a contagem microbiana na saliva foi realizada através do CARITEST SM (Herpo - Produtos Dentários LTDA.). A amostra constou de 200 crianças de 7 a 11 anos de idade, sendo 50 por grupo, nas quais avaliou-se o acúmulo de placa dentária no início e final do experimento. Dessas crianças, foram selecionadas 20 de cada grupo, ao acaso, para as coletas de saliva que foram executadas em 3 etapas: inicial (antes do primeiro bochecho), 24 horas após o primeiro bochecho e uma semana após o último bochecho. Em todos os grupos, as crianças receberam profilaxia profissional antes do início do experimento e seguiram o regime de bochechos diários, com 5 ml de soluçäo, por 1 minuto, durante 4 semanas. Os resultados mostraram uma inibiçäo do acúmulo de placa de 2,89 por cento; 26,75 por cento; 41,20 por cento e 5,91 por cento para os grupos I, II, III e IV, respectivamente. Em relaçäo às faces dentáriaas, os grupos II e III, mostraram maiores reduçöes percentuais para a face vestibular, vindo a seguir a proximal e lingual, sendo que no Grupo II, näo existiu diferença estatisticamente significante entre todas as faces e para o Grupo III, essa diferença foi entre as faces lingual e mesial. Já no Grupo IV, esse resultado foi maior para a face lingual, diferindo estatisticamente apenas da face distal. A soluçäo de digluconato de clorexidina 0,2 por cento registrou menor aceitaçäo pelas crianaças e, juntamente com a soluçäo de gluconato de clorexidina 0,12 por cento associada ao fluoreto de sódio 0,05 por cento, promoveu pigmentaçöes dentárias suaves e semelhantes. Com relaçäo à contagem de estreptococos mutans, devido as crianças apresentarem no início do experimento baixos valores desses microrganismos, os mesmos assim permaneceram, näo existinto diferença estatisticamente significante entre as contagens...

Efectos del captopril en el apetito y la ingestión de alcohol en alcohólicos / Effects of captopril in appetite and alcohol consumption in alcoholics

El captopril ha mostrado la propiedad de disminuir el consumo de alcohol de ratas y también en un ensayo con un grupo de voluntarios sanos. Dada la importancia de esta proyección en la terapéutica de los alcohólicos, decidimos probar sus efectos en un grupo de ellos. La muestra fue un grupo de 14 alcohólicos diagnosticados según criterios DSM-III-R. El ensayo terapéutico fue randomizado, doble ciego y se usó placebo y captopril durante 12 semanas. Los resultados mostraron que ambos tratamientos redujeron significativamente: las cantidades de tragos estándar de alcohol ingeridas, el número de días de embriagueces semanales y de días de apetito alcohólico por semana y la intensidad del apetito. En este período, se embriagaron sólo el 43 por ciento de las veces que sintieron apetito, la gran mayoría de las veces con un apetito de intensidad leve o moderada, y a veces sin apetito. Concluimos que el efecto del captopril y del placebo son semejantes, que el apetito por alcohol no parece decisivo en la ingesta y que la motivación de los pacientes, el apoyo de su familia y del grupo profesional que los atendieron, explicaría los resultados favorables obtenidos